Support is requested to purchase a cryoprobe for an existing 800 MHz NMR spectrometer dedicated to solution-state NMR studies of proteins and marine natural products. By significantly improving the sensitivity of the highest field solution-state NMR spectrometer on the UCSD campus, the cryoprobe will have a broad impact on biomedical research. Not only will the requested instrumentation make new classes of experiments feasible through its combination of high sensitivity and resolution for both 1H and 13C detection, but also it will greatly enhance the overall productivity of the research groups by effectively doubling (or more) the number of experiments that can be performed on an instrument where the requests for time exceed the time available on each monthly schedule. All NIH-supported UCSD investigators whose research involves biomolecular solution-state NMR spectroscopy have contributed to this proposal. With the inclusion of researchers from the Scripps Institute of Oceanography and the new Pharmacy School, the instrumentation will enhance NIH-supported projects in two principal areas of biomedical research: structural biology and marine natural products, which provide complementary routes to new drugs for the treatment of diseases. The relevance of the instrumentation to biomedical research is in two principal areas. The Major Users are involved in structural biology, in particular studies of the structure, dynamics, and folding of proteins, and in drug discovery through the investigation of marine natural products chemistry. The combination of structure-based and medicinal-chemistry based drug design has the potential to lead to new therapeutics for diseases as diverse as cancer, AIDS and other infectious diseases, and inflammatory diseases. [unreadable] [unreadable] [unreadable]